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The process of distillation creates an extract that is pure on a molecular level. If you do a Google search, you will certainly be able to find people who think distillates are too pure, and that full-spectrum oils are more effective.
But in light of the as yet inconclusive evidence, we prefer a distillate. The process of distillation allows the manufacturer an incomparable degree of control over the finished product. We also paid attention to whether artificial flavors were used and we let you know about it.
For this category, we put a lot of weight on how companies deal with third-party lab testing. First, we rated them on how easy it is to find those lab test results COAs — with the highest marks going to companies that go to the trouble of displaying them and keeping them updated on their websites.
We also gave higher points to companies whose COAs give more information than the absolute minimum. All lab tests should test cannabinoid potencies, but we really appreciate companies that also let us see testing results for contaminants like pesticides, heavy metals, and residual solvents.
Nobody can test every single bottle of product, but samples of each product can be tested for cannabinoid potency at a minimum. We then asked how often the companies have third-party testing performed top marks for those who send every batch to a third-party lab.
And we gave points to companies who make it really easy to find information on extraction, sourcing, and growing practices. While quality is super important, most of us have to pay attention to the price of the product as well. So to calculate the product value, we weighed its price against its quality score. For this portion of our research, we went undercover, posing as customers.
We went through the entire shopping experience, beginning with navigating the website and sending out customer service emails and phone calls, and instant messages right through to the checkout process to catch glitches and snags.
We also looked into shipping costs and return policies. And we added a few points for the design and appearance of both the website and bottle. Our updated ranking includes some new companies. So the best product for you may not be the one on the top of our list. We feel confident, though, that all the companies on this ranking are producing high-quality CBD products. All have customer service representatives that should be able to answer any questions you have about their products, and many stand behind their products with strong return policies.
In short, Cannabidiol — or CBD — is a cannabis compound that has many therapeutic benefits. Usually extracted from the leaves and flowers of hemp plants — though marijuana can also be a source — CBD oil is then incorporated into an array of marketable products. These products vary from the most common, like sublingual oils and topical lotions, to the less common think CBD lattes.
Basically, if you can dream it, you can buy it. The endocannabinoid system is spread throughout your brain and body, but primarily throughout your central nervous system. The interaction between cannabinoids and receptors is what produces effects like the regulation of mood, pain, appetite, inflammation, and memory. Plant-based cannabinoids, found in cannabis plants, also interact with the receptors whimsically named CB1 and CB2 in the endocannabinoid system, and each affects your body in different ways.
But CBD is a special snowflake among cannabinoids. This unique interaction creates systemic, whole-body benefits that include, but are by no means limited to:. CBD is a non-psychoactive component of the cannabis plant.
So, no, it will not make you high. There are at least different cannabinoids that can be isolated from cannabis plants, each of which has its own effects. THC or tetrahydrocannabinol is the only cannabinoid responsible for the high that people get from marijuana. This property makes CBD highly useful as a medical treatment for a wide range of conditions. Each cannabinoid has its own properties and confers its own benefits.
Working together, a synergy is created that boosts the healing properties of CBD. The government regulates concentration levels of THC at 0. But THC metabolites are stored in the fat cells of your body, building up over time. If you ever need to take a drug test, this could create an issue for you. CBD Isolate is just that — CBD that has been isolated and then refined to remove all other terpenes, cannabinoids, and plant material. This process eliminates the trace amounts of THC that would otherwise be present.
The result is a fine white powder containing only the pure CBD chemical compound. This isolate is then combined with carrier oils like hemp seed oil or MCT oil to create marketable products. While those in the These terpenes may enhance the effectiveness of CBD — or maybe they just make it smell good. This may be a good place to point out that not all CBD products are created equal.
The industry is still largely unregulated, and the quality and quantity of CBD in a given product will vary wildly. Another point worth clarifying is the difference between hemp seed oil or hemp oil and CBD oil. However, hemp seed oil does not contain any concentration of cannabinoids at all, including CBD. So by all means, stock up at your local natural food store. And now, onto the thorny issue of legality. The simple answer to the question is yes — if it is extracted from hemp.
The Farm Bill established guidelines for growing hemp in the U. CBD derived from marijuana is a different story, and the law varies from state to state. And what research supports these claims? The science behind CBD is in the relatively early stages.
As a cannabinoid, we know that CBD interacts with receptors in your endocannabinoid system. The endocannabinoid system is integrated throughout your body — and this widespread, whole-body interaction creates a broad range of effects.
Hence, the long list of possible benefits. But those who deal with chronic pain know the debilitating, life-sucking reality of this condition. And traditional medications often come with long lists of side effects which can be as debilitating as the pain itself. So when word started getting out that CBD has the potential to reduce pain without those side effects, it seemed too good to be true. In fact, numerous studies have looked at the relationship between CBD and pain, and the results are promising.
Researchers have looked at various kinds of pain — from joint pain to cancer pain. One finding is that CBD increases levels of glutamate and serotonin — both neurotransmitters that play a role in pain regulation. Another field in which CBD is creating a buzz is in the area of mood disorders like anxiety and depression.
Both conditions have been treated with a variety of medications, courtesy of Big Pharma, that have had varying levels of success. Again, the long list of side effects can be off-putting to someone who just wants to get through the day without the sweaty tension of anxiety or the gray haze of depression.
Another study showed CBD to have antidepressant effects comparable to those of the prescription antidepressant Imipramine.
These studies point to the need for more research to be done on CBD. But for those who have had limited success with prescribed medications, talking with your doctor about using CBD as an alternative is worth consideration.
We exercise, we avoid things that we really, really want — like naps and caffeine. And still, the magic escapes us. But help is near. CBD, with its calming, anti-anxiety effects, is helping many people get the sleep they need — without the groggy side effects of many sleeping pills.
There are lots of things that can keep a person awake — from anxiety or depression to chronic pain. In the United States, over 3 million people suffer from epilepsy — , of those people are children. Epilepsy is a disorder of the brain that causes seizures — of which there are over thirty different kinds, ranging from mild and infrequent to life-threatening. Not surprisingly, people with epilepsy face significant challenges — from the cost of healthcare to work limitations and social isolation.
And treatment proves difficult for many people. In fact, over one-third of people with epilepsy live with uncontrollable seizures because there is no available treatment that works for them. So when CBD started gaining mainstream attention for stopping or greatly reducing seizures, people started to get very excited. And with good reason. Evidence from laboratory studies , small clinical studies , and anecdotal reports over a number of years suggest that CBD helps control seizures.
And in June of , a major advance was made when the FDA approved a prescription cannabidiol medicine — Epidiolex — to treat rare and severe forms of epilepsy. This means that people with these rare and devastating forms of epilepsy will have access to CBD that has been clinically tested and dosed.
This is a hugely beneficial effect of CBD. 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. Psychosis The review by Bergamaschi et al. Addiction A case study describes a patient treated for cannabis withdrawal according to the following CBD regimen: Endocrine effects and glycemic including appetite effects To the best of our knowledge, no acute studies were performed that solely concentrated on CBD glycemic effects.
Physiological effects A first pilot study in healthy volunteers in by Mincis et al. Neurological and neuropsychiatric effects Anxiety 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. Psychosis and bipolar disorder In a 4-week open trial, CBD was tested on Parkinson's patients with psychotic symptoms. Conclusion This review could substantiate and expand the findings of Bergamaschi et al.
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Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: Distinct effects of D9-tetrahydro-cannabinoland cannabidiol on neural activation during emotional processing. Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans. Inhibition and induction of human cytochrome P CYP enzymes.
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Cannabidiol enhances xenobiotic permeability through the human placental barrier by direct inhibition of breast cancer resistance protein: Am J Obstet Gynecol. Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice.
Cannabidiol, among other cannabinoid drugs, modulates prepulse inhibition of startle in the SHR animal model: Cannabidiol attenuates sensorimotor gating disruption and molecular changes induced by chronic antagonism of NMDA receptors in mice. Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania. Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances.
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Cannabidiol arrests onset of autoimmune diabetes in NOD mice.
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