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This led to amelioration of learning effects in a pharmacological model of AD. The chronic study we want to describe in more detail here used a transgenic mouse model of AD, where 2. CBD was able to prevent the development of a social recognition deficit in the AD transgenic mice.
Using statistical analysis by analysis of variance, this was shown to be only a trend. This might have been caused by the high variation in the transgenic mouse group, though. This was probably due to already elevated cholesterol in the transgenic mice.
The study observed no side effects. After CBD treatment was stopped, observation continued until the mice were 24 weeks old. CBD increased IL levels, which is thought to act as an anti-inflammatory cytokine in this context. After inducing arthritis in rats using Freund's adjuvant, various CBD doses 0. CBD reduced joint swelling, immune cell infiltration. CBD was shown to be able to influence migratory behavior in cancer, which is also an important aspect of embryogenesis. Helix-loop-helix Id proteins play a role in embryogenesis and normal development via regulation of cell differentiation.
High Id1-levels were also found in breast, prostate, brain, and head and neck tumor cells, which were highly aggressive. In contrast, Id1 expression was low in noninvasive tumor cells. Id1 seems to influence the tumor cell phenotype by regulation of invasion, epithelial to mesenchymal transition, angiogenesis, and cell proliferation. There only seems to exist one study that could not show an adverse CBD effect on embryogenesis.
An in vitro study could show that the development of two-cell embryos was not arrested at CBD concentrations of 6. Various studies have been performed to study CBD anticancer effects.
CBD every 3 days for a total of 28 weeks, almost completely reduced the development of metastatic nodules caused by injection of human lung carcinoma cells A in nude mice. The typical side effects of traditional anticancer medication, emesis, and collateral toxicity were not described in these studies. Consequently, CBD could be an alternative to other MMP1 inhibitors such as marimastat and prinomastat, which have shown disappointing clinical results due to these drugs' adverse muscoskeletal effects.
Two studies showed in various cell lines and in tumor-bearing mice that CBD was able to reduce tumor metastasis. CBD downregulated Id1 at promoter level and reduced tumor aggressiveness. Moreover, to carry out these experiments, animals are often immunologically compromised, to avoid immunogenic reactions as a result to implantation of human cells into the animals, which in turn can also affect the results.
Another approach was chosen by Aviello et al. After 3 months, the number of aberrant crypt foci, polyps, and tumors was analyzed. The high CBD concentration led to a significant decrease in polyps and a return to near-normal levels of phosphorylated Akt elevation caused by the carcinogen. Animal studies summarized by Bergamaschi et al. Chronic administration 14 days, 2.
This effect could be inhibited by coadministration of a CB2R antagonist. The positive effects of CBD on hyperglycemia seem to be mainly mediated via CBD anti-inflammatory and antioxidant effects.
In addition, treatment increased adiponectin and liver glycogen concentrations. CBD showed inhibition of testosterone oxidation in the liver. Motor function was also tested on a rotarod, which was also not affected by CBD administration.
Static beam performance, as an indicator of sensorimotor coordination, showed more footslips in the CBD group, but CBD treatment did not interfere with the animals' speed and ability to complete the test. Compared to other anticonvulsant drugs, this effect was minimal. CBD did not lead to adverse effects. In addition, psychomotor function and psychological functions were not disturbed.
Interestingly, the CYP2C19 inhibitor omeprazole, used to treat gastroesophageal reflux, could not significantly affect the pharmacokinetics of CBD. Unfortunately, it was not mentioned whether this effect was mediated via the cytochrome P complex.
Another aspect, which has not been thoroughly looked at, to our knowledge, is that several cytochrome isozymes are not only expressed in the liver but also in the brain. It might be interesting to research organ-specific differences in the level of CBD inhibition of various isozymes. Apart from altering the bioavailability in the overall plasma of the patient, this interaction might alter therapeutic outcomes on another level.
Generally, more human studies, which monitor CBD-drug interactions, are needed. In a double-blind, placebo-controlled crossover study, CBD was coadministered with intravenous fentanyl to a total of 17 subjects. This was followed by a single 0. This extensive tool tests, for example, 78 adverse effects divided into 23 categories corresponding to organ systems or body parts. No respiratory depression or cardiovascular complications were recorded during any test session. The results of the evaluation of pharmacokinetics, to see if interaction between the drugs occurred, were as follows.
No effect was evident for urinary CBD and metabolite excretion except at the higher fentanyl dose, in which CBD clearance was reduced. Importantly, fentanyl coadministration did not produce respiratory depression or cardiovascular complications during the test sessions and CBD did not potentiate fentanyl's effects.
No correlation was found between CBD dose and plasma cortisol levels. CBD did not worsen the adverse effects e. Coadministration was safe and well tolerated, paving the way to use CBD as a potential treatment for opioid addiction. A Dutch study compared subjective adverse effects of three different strains of medicinal cannabis, distributed via pharmacies, using VAS. The 12 adjectives used for this study were as follows: This strain showed significantly lower levels of anxiety and dejection.
Moreover, appetite increased less in the high CBD strain. The review by Bergamaschi et al. This holds especially true for the extrapyramidal motor side effects elicited by classical antipsychotic medication.
Order of drug administration was pseudorandomized across subjects, so that an equal number of subjects received any of the drugs during the first, second, or third session in a double-blind, repeated-measures, within-subject design. This effect was caused by opposite neural activation of relevant brain areas. In addition, no effects on peripheral cardiovascular measures such as heart rate and blood pressure were measured.
A randomized, double-blind, crossover, placebo-controlled trial was conducted in 16 healthy nonanxious subjects using a within-subject design. The doses were selected to only evoke neurocognitive effects without causing severe toxic, physical, or psychiatric reactions. The physiological parameters, heart rate and blood pressure, were also monitored and no significant difference between the placebo and the CBD group was observed.
A case study describes a patient treated for cannabis withdrawal according to the following CBD regimen: Hepatic enzymes were also measured daily, but no effect was reported. Naturalistic studies with smokers inhaling cannabis with varying amounts of CBD showed that the CBD levels were not altering psychomimetic symptoms. CBD might work to alleviate disorders of addiction, by altering the attentive salience of drug cues.
The study did not further measure side effects. CBD can also reduce heroin-seeking behaviors e. This was shown in the preclinical data mentioned earlier and was also replicated in a small double-blind pilot study with individuals addicted to opioids, who have been abstinent for 7 days. One hour after the video session, subjective craving was already reduced after a single CBD administration.
The effect persisted for 7 days after the last CBD treatment. Interestingly, anxiety measures were also reduced after treatment, whereas no adverse effects were described. A pilot study with 24 subjects was conducted in a randomized, double-blind, placebo-controlled design to evaluate the impact of the ad hoc use of CBD in smokers, who wished to stop smoking. Pre- and post-testing for mood and craving of the participants was executed. Craving was assessed using the Tiffany Craving Questionnaire On day 1 and 7, exhaled CO was measured to test smoking status.
Sedation, depression, and anxiety were evaluated with the MRS. At day 7, the anxiety levels for placebo and CBD group did not differ. CBD did not increase depression in contrast to the selective CB1 antagonist rimonabant.
CBD might weaken the attentional bias to smoking cues or could have disrupted reconsolidation, thereby destabilizing drug-related memories. To the best of our knowledge, no acute studies were performed that solely concentrated on CBD glycemic effects. Moreover, the only acute study that also measured CBD effect on appetite was the study we described above, comparing different cannabis strains.
Growth hormone and prolactin levels were unchanged. Compared to the healthy individuals, the cortisol levels increased less after TSST in the 32 at-risk individuals. The CBD group showed less reduced cortisol levels but differences were not significant. Truly chronic studies with CBD are still scarce. Nonetheless, we also included these studies with repeated CBD treatment, because we think that compared to a one-time dose of CBD, repeated CBD regimens add value and knowledge to the field and therefore should be mentioned here.
These results are supported by another study described in the review by Grotenhermen et al. CBD was administered on average with three other drugs, including clobazam The coadministration led to an alteration of blood levels of several antiepileptic drugs. In the case of clobazam this led to sedation, and its levels were subsequently lowered in the course of the study. A first pilot study in healthy volunteers in by Mincis et al.
Clinical chronic lasting longer than a couple of weeks studies in humans are crucial here but were mostly still lacking at the time of writing this review. They hopefully will shed light on the inconsistencies observerd in animal studies. Chronic studies in humans may, for instance, help to test whether, for example, an anxiolytic effect always prevails after chronic CBD treatment or whether this was an artifact of using different animal models of anxiety or depression.
In a 4-week open trial, CBD was tested on Parkinson's patients with psychotic symptoms. This led to a reduction of their psychotic symptoms. Moreover, no serious side effects or cognitive and motor symptoms were reported. No adverse effects were observed and her symptoms improved. The same positive outcome was registered in another study described by Bergamaschi et al. The respective treatment was maintained for three additional weeks.
This was the case for three patients in the CBD group and five patients in the amisulpride group. CBD treatment was accompanied by a substantial increase in serum anandamide levels, which was significantly associated with clinical improvement, suggesting inhibition of anandamide deactivation via reduced FAAH activity. In addition, the FAAH substrates palmitoylethanolamide and linoleoyl-ethanolamide both lipid mediators were also elevated in the CBD group.
CBD showed less serum prolactin increase predictor of galactorrhoea and sexual dysfunction , fewer extrapyramidal symptoms measured with the Extrapyramidal Symptom Scale, and less weight gain. Moreover, electrocardiograms as well as routine blood parameters were other parameters whose effects were measured but not reported in the study. CBD better safety profile might improve acute compliance and long-term treatment adherence.
A press release by GW Pharmaceuticals of September 15th, , described 88 patients with treatment-resistant schizophrenic psychosis, treated either with CBD in addition to their regular medication or placebo.
Important clinical parameters improved in the CBD group and the number of mild side effects was comparable to the placebo group. Moreover, neurological and physiological examinations were performed, which neither showed signs of CBD toxicity nor severe side effects. The study also illustrated that CBD was well tolerated. CBD in addition to their regular epilepsy medication. Another clinical study lasting at least 3 months with children and young adults with various forms of epilepsy, who were treated with the CBD drug Epidiolex, was presented at the American Academy for Neurology in In a few cases, severe side effects occurred, but it is not clear, if these were caused by Epidiolex.
The largest CBD study conducted thus far was an open-label study with Epidiolex in patients mainly children, the average age of the participants was 11 suffering from severe epilepsy, who could not be treated sufficiently with standard medication. Ten percent of the patients reported side effects tiredness, diarrhea, and exhaustion.
After extensive literature study of the available trials performed until September , CBD side effects were generally mild and infrequent. The only exception seems to be a multicenter open-label study with a total of patients aged 1—30 years, with treatment-resistant epilepsy.
This led to a reduction in seizure frequency. It is therefore difficult to put the side effect frequency into perspective. Attributing the side effects to CBD is also not straightforward in severely sick patients.
Thus, it is not possible to draw reliable conclusions on the causation of the observed side effects in this study. This rating instrument comprised the following factors: This assessment instrument analyzes adverse medication effects, including psychic, neurologic, autonomic, and other manifestations.
Using various safety outcome variables, clinical tests, and the cannabis side effect inventory, it was shown that there were no differences between the placebo group and the CBD group in the observed side effects. The occurrence of various degrees of GVHD was compared with historical data from patients, who had only received the standard treatment. This resulted in lower resistin levels compared to baseline. The hormone resistin is associated with obesity and insulin resistance.
Compared to baseline, glucose-dependent insulinotropic peptide levels were elevated after CBD treatment. This incretin hormone is produced in the proximal duodenum by K cells and has insulinotropic and pancreatic b cell preserving effects. CBD was well tolerated in the patients. However, with the comparatively low CBD concentrations used in this phasetrial, no overall improvement of glycemic control was observed. When weight and appetite were measured as part of a measurement battery for side effects, results were inconclusive.
For instance, the study mentioned above, where 23 children with Dravet syndrome were treated, increases as well as decreases in appetite and weight were observed as side effects.
However, in the safety analysis group, consisting of subjects, 10 showed decreased weight and 12 had gained weight. Both these factors were not controlled for in the reviewed studies. This review could substantiate and expand the findings of Bergamaschi et al. First, more studies researching CBD side effects after real chronic administration need to be conducted.
Many so-called chronic administration studies, cited here were only a couple of weeks long. Second, many trials were conducted with a small number of individuals only. To perform a throrough general safety evaluation, more individuals have to be recruited into future clinical trials.
Third, several aspects of a toxicological evaluation of a compound such as genotoxicity studies and research evaluating CBD effect on hormones are still scarce. Especially, chronic studies on CBD effect on, for example, genotoxicity and the immune system are still missing. Last, studies that evaluate whether CBD-drug interactions occur in clinical trials have to be performed. In conclusion, CBD safety profile is already established in a plethora of ways.
However, some knowledge gaps detailed above should be closed by additional clinical trials to have a completely well-tested pharmaceutical compound. The study was commissioned by the European Industrial Hemp Association. EIHA paid nova-Institute for the review. Iffland K, Grotenhermen F An update on safety and side effects of cannabidiol: National Center for Biotechnology Information , U. Journal List Cannabis Cannabinoid Res v. Published online Jun 1.
Find articles by Kerstin Iffland. Find articles by Franjo Grotenhermen. Author information Copyright and License information Disclaimer. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This article has been cited by other articles in PMC. Relevant Preclinical Studies Before we discuss relevant animal research on CBD possible effects on various parameters, several important differences between route of administration and pharmacokinetics between human and animal studies have to be mentioned.
Open in a separate window. The reality is more complex, because CBD is lipophilic and, for example, will consequently accumulate in fat tissue. These calculations were made with the intention to give the reader an impression and an approximation of the supraphysiological levels used in in vitro studies. CBD-drug interactions Cytochrome Pcomplex enzymes This paragraph describes CBD interaction with general drug -metabolizing enzymes, such as those belonging to the cytochrome P family.
Neurological and neurospychiatric effects Anxiety and depression Some studies indicate that under certain circumstances, CBD acute anxiolytic effects in rats were reversed after repeated day administration of CBD. Psychosis and bipolar disorder Various studies on CBD and psychosis have been conducted. Addiction CBD, which is nonhedonic, can reduce heroin-seeking behavior after, for example, cue-induced reinstatement.
Neuroprotection and neurogenesis There are various mechanisms underlying neuroprotection, for example, energy metabolism whose alteration has been implied in several psychiatric disorders and proper mitochondrial functioning. Immune system Numerous studies show the CBD immunomodulatory role in various diseases such as multiple sclerosis, arthritis, and diabetes.
Cell migration Embryogenesis CBD was shown to be able to influence migratory behavior in cancer, which is also an important aspect of embryogenesis. Cancer Various studies have been performed to study CBD anticancer effects. Food intake and glycemic effects Animal studies summarized by Bergamaschi et al. Genotoxicity and mutagenicity Jones et al. Acute Clinical Data Bergamaschi et al. Physiological effects In a double-blind, placebo-controlled crossover study, CBD was coadministered with intravenous fentanyl to a total of 17 subjects.
Side effects and safety concerns: CBD can cause side effects and interact with certain medications and conditions, although these effects have typically been reported only with very high daily intake, i.
Simply provide an email address below. You must provide a valid email address. Send me a copy. Your message has been sent. They sell both water and gummies. I have a teenage daughter with anxiety, and she won't take pills and the taste of the oil will be difficult to get her to take. I bought a bottle, but now strongly suspect that I was robbed, hood-winked and too trusting. Could you please test and review this product?
You will also see that there are more cost-effective products in terms of getting CBD. I have anterior rotation of my hips, and recently 'put out my back' I woke up in the morning pain free! I am a competitive athlete, and so need to be mobile.
I am now in desperate search for a high concentration of CBD oil that I can massage directly into my muscles rather than paying an outrageous amount of money for someone to blend together with coconut oil and menthol into a topical cream and put into a deceptive container the container has a smaller container inside that contains the actual cream so you are getting half the amount that you think you are getting from looking at the container.
It also contains smaller but not quantified amounts of Natural Emolients and Hemp Extract. It's not at all clear how much hemp extract is in the product, let alone the amount of CBD in the hemp extract. It's possible that you are getting relief from the other ingredients. Is it either ignorance of how to process the material or outright fraud? The brand is The Raw Food World brand. Great results, would love to see a Consumer Labs review of their products.
I was referred to this company by a Vet Oncologist for my dog who had bone cancer. It really helped with her pain and provided sedation.
The company claims that every batch that they produce is reviewed by a third party which provides a Certificate of Analysis. Results are in our report at https: It seemed the FDA were fussing about labelling and claims more than anything. They sent warning letters to CBD companies about non-compliance in this regard.
However, they also, very kindly, published a list of test results for quite a few popular companies. This seemed to be of no interest whatsoever to the FDA again, they were in a tiz about the labels but it is very useful for us consumers.
Charlotte's Web was in trouble for the claims they make and for their 'Realm of Caring' website not being transparent about its commercial connections. Personally, the one and only thing I care about in regards to buying CBD products is - what is in the bottle. And, dear Consumer Lab, this is hopefully where you will come in, and give us some guidance.
The sooner the better. In contrast the Elixinol CBD Hemp oil did not seem to provide the same benefits and after days of continued use made me a bit nauseous, however it may have been a coincidence.
I am very interested in seeing a report that shows how much CBD is actually in these products, any possible contaminant levels and uses for these tinctures. I have significant relief from pain and fatigue at a cost I can afford. I found Lazarus Naturals to be the least expensive.
More and more people are trying this helpful supplement and it's making the pharmaceutical companies nervous. There are so many companies jumping on this CBD oil bandwagon, that people don't know what to buy, or if they should. There is a lot of information available on Google. I no longer trust the FDA. The Lazarus Naturals works well for me for severe arthritis in my back and hips. I like the fact that they post their independent lab results for each batch. I wish all CBD oil companies would do that.
It is produced by The Stanley Brothers in Colorado. That doesn't concern me. Hemp Extract, tinture mg? They have a batch analysis performed on all of their products. Many medication protocols were tried and nothing made much of a difference. It was awful for him. He is a whole different bird, capapble of relaxing and being affectionate and enjoying his life I am happy beyond words that CBD is available to help this parrot - nothing else helped him.
This parrot has been getting CBD for about 6 months now and it continues to be very effective. I had his bloodwork checked recently - no signs of liver or kidney side effects. It has been reccomended for both of us. It's pricey, but I'm willing to spend on it if IRS worth it. I've been a consumer lab subscriber for many many years. Thank you for the work you do. CV Sciences, formerly Cannavest, seem to be behind many of the questionable products, but they operate under so many brand names, it is impossible to keep up.
The advise is always to ask for independent test results before buying - but really a company could send one thing to a lab, and something else to customers. Out of interest, I started my research because I bought some CBD paste to try for my crippling arthritis pain.
It was horribly expensive and came from a guy, who knew a guy, who said it was really Endoca, but had no labels. It really worked so well, I stopped Mobic and was walking without a brace.
The shady guys had been shut down when I went to reorder. I also discovered that Endoca is not available in Australia where I live. Hence my research into something hopefully as good who knows what I had and even more hopefully, at an affordable price. Now I have spent so much money experimenting, I could have bought a return ticket to personally visit Mr. Endoca and buy up half his stock. Please, please Consumer Lab can you get on to testing for us?
I know I am not alone in my frustration at how hard it is to know what's what in this industry. I use the rubs for severe spinal stenosis and arthritis. My doctor says Young Liiving's Copaiba oil has a higher concentration of pain relief. Is there a difference between "dietary supplements" and "supplements" - this distinction appears to be made here in the review as to legality? Or is this reference to legality only referring to the difference between industrial hemp derived CBD and the medical marijuana controlled plant?
I've noticed an explosion of CBD products, hemp oils, etc. Could you clarify in a more obvious way these subtle points. Medical use of CBD is legal in many, but not all, states, as noted above, but the products cannot necessarily be legally sold in those same states. Hope that helps a bit.
It is tricky and evolving area. It is still not clear to me. Tricky is an understatement. It appears that it was the DEA that put it on schedule 1 in Dec. DEA" legal case 14 years ago, it is being challenged again? What I don't understand is how it can illegal, yet sold nearly everywhere, at the same time? It is illegal and legal at the same time? A kind, generous friend gave my wife a bottle to help with her RA symptoms while we were vacationing in Canada.
She will not use it until we find out if it is legal to possess and her doctors give her the go ahead, but we would be interested in the test results. I have been a Consumerlab member for years. We will consider that. We have received many suggestions this week of products. He has arthritis and a bad heart murmur. At first it really seemed to help with his pain and he was much more mobile. After a few weeks he started getting more lethargic and not eating. I did some research and discovered it should not be given along with any medications that are metabolized by the liver.
It causes these meds to build up in the body so he was exhibiting symptoms of overdose of his heart medications. I stopped the CBD oil and he got started eating and seemed to feel better.
Give with caution if your pet is on other meds. You can read the manufacturer's claims. I'm 87 and found the CBD oil does relieve my aches and pains, and clears my mind. The results aren't like prescription drugs; they aren't usually immediate.
People have differing results. There are recommendations for the amount to take and you are wise to heed them. I use Blubird Botanicals and ran out a couple days ago, and I can definitely feel the difference. I expect a new order tomorrow. For me, the expense is worth it. There are several online sites where you can receive much information. Beware of the Pure Natural brand.
It offers a free trial, but in the small print you are signing up for a monthly supply at full cost. The BBB has a report on this. Please note that hemp oil may be made with hemp seeds or other parts of the plant.
Commonly hempseed oil is called hemp oil. I meant to say that CBD oil isn't made from the seeds, from what I've read. I am being ask about CBD frequently now. This is what one of my clients had to say about it. I bought it at the Remedy Pharmacy in Torrance on Hawthorne Boulevard, but you can also order online. I didn't have incredible overnight success with it like the women at the seminar we went to did, but I am having less pain and sleeping better.
I don't know if it's a true change or just placebo effect, but I'll take it either way: The pain is along, above and below the scar area.
1. LEARN THE CBD BASICS
CBD and Hemp Oils Reviewed by cstore.me and abnormal results on liver-function tests (Devinsky, New Eng J Med ). Published online Jun 1. doi: /can PMCID: Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug. CBD oil and arthritis pain relief A study found that CBD might be a safe and useful treatment for OA joint.