CBD oil is a natural remedy derived from the cannabis plant. status as an illegal Schedule 1 drug, research on CBD oil is still in its infancy. Analyzing several trials and studies, a report concluded that adults treated. Geneva, November Page 2. 39th ECDD () Agenda item Cannabidiol (CBD). Page 2 .. Listing on the WHO Model List of Essential Medicines. . There is unsanctioned medical use of CBD based products with oils, supplements, gums, and (+)-CBD is likely to cause THC-like psychoactive effects. D. 15, -- A compound found in the cannabis plant is not harmful, has health and human studies, the committee concludes that "In humans, CBD exhibits no effects . In the U.S., CBD is a Schedule 1 controlled substance. CBD is an ingredient in popular products sold over the counter as oils, extracts.
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The Cannabis Health Index CHI is an evidence-based scoring system for cannabis in general, not just CBD effects and its effectiveness on various health issues based on currently available research data. Using this rubric and based on twenty-one studies, cannabis rated in the possible-to-probable range of efficacy for treatment of depression. Research in called for clinical trials to look into the effectiveness of cannabinoids for bipolar disorder manic depression.
It also works on the GABA-glutamate system and the hypothalamic-pituitary-adrenal axis. Its main role is restoring balance through inhibition when levels are too high and enhancement when they are too low.
This is the most likely reason phytocannabinoids in general and CBD specifically are able to regulate depression and anxiety. The scientific inquiry into cannabis over the past several decades has confirmed that it is an effective and safe analgesic for many kinds of pain. Of all the reasons that people use CBD today, pain is the most common. The same can be said of cannabis in general. In the United States, over seventy million people suffer from chronic pain, which is defined as experiencing over one hundred days per year of pain.
Physicians differentiate between neuropathic usually chronic and nociceptive pains usually time-limited , and cannabis works on most neuropathic and many nociceptive types of pain. A number of studies have demonstrated that the endocannabinoid system is both centrally and peripherally involved in the processing of pain signals. Cannabinoids can be used along with opioid medications, and a number of studies have demonstrated that they can reduce the amount of opioids needed, lessen the buildup of tolerance, and reduce the severity of withdrawal.
It is suggested that patients work with a health care practitioner experienced in recommending CBD oil or medicinal cannabis so that dosage and delivery methods can be developed and fine-tuned on an individual basis.
Oral CBD products with a ratio of Most discussions of treating pain with CBD suggest that finding the right dosage is critical. Always start with the micro dose to test sensitivity and go up as needed within the dosing range by body weight until symptoms subside. If CBD-dominant products alone are not enough to treat a particular case, products with a higher ratio of THC are sometimes recommended to better manage pain.
For day use, more stimulating, sativa varieties with higher concentrations of myrcene could be added to the formula. In general, for pain, and especially for evening and nighttime, indica strains are favored for their relaxing, sedative effect. A person without experience with THC should use caution and titrate slowly up to higher doses.
Research as well as patient feedback have indicated that, in general, a ratio of 4: THC is the most effective for both neuropathic and inflammatory pain. Each individual is different, however—for some, a 1: Chemotypes high in beta-caryophyllene, myrcene, and linalool provide additional pain relief and increase the effectiveness of other cannabinoids for analgesia. For relief of immediate symptoms, as in a flare-up of pain, vaporizing or smoking work well.
The medication effect is immediate and lasts one to three hours, whereas most ingested products take thirty to sixty minutes before taking effect faster on an empty stomach and last six to eight hours. Sublingual sprays or tinctures taken as liquid drops also take effect quickly and last longer than inhaled products.
When pain is localized, topical products can be applied. Topicals affect the cells near application and through several layers of tissue but do not cross the blood-brain barrier and are, therefore, not psychoactive. The skin has the highest amount and concentration of CB2 receptors in the body.
Considering all of the studies together, which number over forty for various types of pain , CBD and cannabis are shown to have a rating of likely probable efficacy. It is one of the best-substantiated medical uses of cannabinoids. Sativex, a cannabis plant—derived oromucosal spray containing equal proportions of THC and CBD, has been approved in a number of countries for use to treat specific types of pain. Numerous randomized clinical trials have demonstrated the safety and efficacy of Sativex for treatment of central and peripheral neuropathic pain, rheumatoid arthritis, and cancer pain.
A study showed that CBD and CBC stimulated descending pain-blocking pathways in the nervous system and caused analgesia by interacting with several target proteins involved in nociceptive control. Sleep Disorders Insomnia, Sleep Apnea Cannabis and sleep have a complex relationship that is only beginning to be understood by science.
In general, for most people, indica strains are more relaxing and effective for sleep disorders, whereas sativa strains are more stimulating and tend to keep people awake. Several studies conducted between and demonstrated the variable effect of different cannabinoids on sleep. Another study found CBD to be wake-inducing for most subjects, though some reported better sleep a few hours after taking it. However, a significant number of people find THC, even indica strains, will make the mind more active.
For these people, CBD oil can benefit them and tends to work well, providing the relaxation and calm for the mental as well as the physical body. For these people, CBD taken at nighttime as part of a bedtime regime produces a restful sleep, not the alertness produced in the daytime.
This bidirectional effect of CBD is the result of balancing the endocannabinoid system. In relation to sleep apnea, a animal study observed the ability of THC to restore respiratory stability by modulating serotonin signaling and reducing spontaneous sleep-disordered breathing.
It is suggested that patients work with a health care practitioner experienced in recommending CBD or medicinal cannabis so that dosage and delivery methods can be developed and fine-tuned on an individual basis. As mentioned previously, while CBD-dominant products help some people sleep, in others it promotes wakefulness. These tend to be high in myrcene and linalool, a terpene shared with lavender and known to be effective for relaxation. Cannabis combinations with ratios of 1: THC can be used when patients want to reduce psychoactivity.
Oral consumption is recommended as it usually lasts the whole night. The micro to standard dose is usually recommended to treat insomnia and sleep apnea. When relaxing indica strains are used with higher THC levels, a dose of 5—10 mg is usually sufficient.
Other people find they need larger doses, such as 15—40 mg. CBD taken as a tincture or edible will aid in a restful six to seven hours of sleep. This type of disorder varies widely from one patient to the next. Often, one needs to perform some experimental research and try strains of different CBD: For immediate medicinal effects, vaporizing or smoking work well.
This can be helpful for either initial sleep onset or for wakefulness in the middle of a rest period but only lasts one to three hours. The medication effect is immediate, whereas most ingested products take thirty to sixty minutes before taking effect faster on an empty stomach and last six to eight hours.
Vaporizers that use a cartridge filled with the CO2 concentrate are convenient and highly effective, and these are available in various ratios of CBD to THC. Using this rubric, the use of cannabis-based products for treating insomnia has a rating of likely probable efficacy based on the four studies available at press time 3. A study with the pharmaceutical 1: THC spray showed good results in helping patients with chronic pain sleep better.
Four patients in a case series treated with CBD in had prompt and substantial reduction in the frequency of RBD-related events without side effects. The Dana Forum on Brain Science Trends in Pharmacological Science 36, no. Ashton and Paul F. Van Den Eeden, G. Van Bockstaele New York: Springer, , — Ameritox, , www. Radulovacki, and David W. Leonard Leinow has three decades of experience growing and studying medical cannabis and brings a unique spiritual perspective to his work.
In , he formed Synergy Wellness, a not-for-profit medical cannabis collective in California. Synergy Wellness has over 3, members in its collective and is an artisan organization making hand-crafted organic and natural whole plant-based products. They are specialists in CBD cannabidiol , the non-psychoactive portion of cannabis, and are pioneers in this aspect of the industry. Leinow is known for his proprietary blends of tinctures and medicine used for cancer and epilepsy patients.
Juliana Birnbaum is trained as a cultural anthropologist and skilled in four languages and has lived and worked in the U. She was the first graduate of the Cornerstone Doula School, one of the most rigorous natural birth programs in the U. She is engaged variously as writer, editor, teacher, midwife assistant and mother when not attempting new yoga poses or learning how to garden.
Free Enlightened Living Course: This paragraph describes CBD interaction with general drug -metabolizing enzymes, such as those belonging to the cytochrome P family. This might have an effect for coadministration of CBD with other drugs. Various drugs such as ketoconazol, itraconazol, ritonavir, and clarithromycin inhibit this enzyme. It has to be pointed out though, that the in vitro studies used supraphysiological CBD concentrations.
Studies in mice have shown that CBD inactivates cytochrome P isozymes in the short term, but can induce them after repeated administration. This is similar to their induction by phenobarbital, thereby implying the 2b subfamily of isozymes. Hexobarbital is a CYP2C19 substrate, which is an enzyme that can be inhibited by CBD and can consequently increase hexobarbital availability in the organism. Recorcinol was also found to be involved in CYP induction. CYP1A1 can be found in the intestine and CBD-induced higher activity could therefore prevent absorption of cancerogenic substances into the bloodstream and thereby help to protect DNA.
This means that they do not reduce CBD transport to the brain. The same goes for gefitinib inhibition of Bcrp. These proteins are also expressed at the blood—brain barrier, where they can pump out drugs such as risperidone.
This is hypothesized to be a cause of treatment resistance. Nicardipine was used as the BCRP substrate in the in vitro studies, where the Jar cell line showed the largest increase in BCRP expression correlating with the highest level of transport. The ex vivo study used the antidiabetic drug and BCRP substrate glyburide. In this study, a dose—response curve should be established in male and female subjects CBD absorption was shown to be higher in women because the concentrations used here are usually not reached by oral or inhaled CBD administration.
Nonetheless, CBD could accumulate in organs physiologically restricted via a blood barrier. Some studies indicate that under certain circumstances, CBD acute anxiolytic effects in rats were reversed after repeated day administration of CBD. Nonetheless, the behavioral tests for OBX-induced hyperactivity and anhedonia related to depression and open field test for anxiety in the CBD-treated OBX animals showed an improved emotional response.
Using microdialysis, the researchers could also show elevated 5-HT and glutamate levels in the prefrontal cortex of OBX animals only. This area was previously described to be involved in maladaptive behavioral regulation in depressed patients and is a feature of the OBX animal model of depression. The fact that serotonin levels were only elevated in the OBX mice is similar to CBD differential action under physiological and pathological conditions.
A similar effect was previously described in anxiety experiments, where CBD proved to be only anxiolytic in subjects where stress had been induced before CBD administration.
Elevated glutamate levels have been proposed to be responsible for ketamine's fast antidepressant function and its dysregulation has been described in OBX mice and depressed patients.
Chronic CBD treatment did not elicit behavioral changes in the nonoperated mice. No adverse effects were reported in this study. Various studies on CBD and psychosis have been conducted. The two higher CBD doses had beneficial effects comparable to the atypical antipsychotic drug clozapine and also attenuated the MK effects on the three markers mentioned above.
The publication did not record any side effects. One of the theories trying to explain the etiology of bipolar disorder BD is that oxidative stress is crucial in its development.
Whereas CBD did not have an effect on locomotion, it did increase brain-derived neurotrophic factor BDNF levels and could protect against amphetamine-induced oxidative damage in proteins of the hippocampus and striatum. No adverse effects were recorded in this study. Another model for BD and schizophrenia is PPI of the startle reflex both in humans and animals, which is disrupted in these diseases.
CBD, which is nonhedonic, can reduce heroin-seeking behavior after, for example, cue-induced reinstatement. In addition, the described study was able to replicate previous findings showing no CBD side effects on locomotor behavior.
There are various mechanisms underlying neuroprotection, for example, energy metabolism whose alteration has been implied in several psychiatric disorders and proper mitochondrial functioning. A study comparing acute and chronic CBD administration in rats suggests an additional mechanism of CBD neuroprotection: Mitochondrial activity was measured in the striatum, hippocampus, and the prefrontal cortex.
Since the mitochondrial complexes I and II have been implied in various neurodegenerative diseases and also altered ROS reactive oxygen species levels, which have also been shown to be altered by CBD, this might be an additional mechanism of CBD-mediated neuroprotection. In healthy cells, this can be interpreted as a way to protect against the higher ROS levels resulting from more mitochondrial activity.
Another publication studied the difference of acute and chronic administration of two doses of CBD in nonstressed mice on anxiety. Already an acute i. Fifteen days of repeated i. However, the higher dose caused a decrease in neurogenesis and cell proliferation, indicating dissociation of behavioral and proliferative effects of chronic CBD treatment.
The study does not mention adverse effects. Numerous studies show the CBD immunomodulatory role in various diseases such as multiple sclerosis, arthritis, and diabetes.
These animal and human ex vivo studies have been reviewed extensively elsewhere, but studies with pure CBD are still lacking. It would be especially interesting to study when CBD is proinflammatory and under which circumstances it is anti-inflammatory and whether this leads to side effects Burstein, Table 1 shows a summary of its anti-inflammatory actions; McAllister et al.
In case of Alzheimer's disease AD , studies in mice and rats showed reduced amyloid beta neuroinflammation linked to reduced interleukin [IL]-6 and microglial activation after CBD treatment. 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:
8 Science-Based Benefits of Cannabis-Based CBD Oil (The Government Won’t Tell You About)
The list of CBD oil benefits and health concerns treatable by CBD is so long . lasts one to three hours, whereas most ingested products, including CBD oil, take .. Moskowitz MD, personal communication with the authors, February 2, CBD, or cannabidiol, oil is currently being studied for its health benefits. CBD oil benefits list . This is partially because Schedule 1 substances like cannabis are highly regulated, causing Medically reviewed by Debra Rose Wilson, PhD, MSN, RN, IBCLC, AHN-BC, CHT on April 10, — Written by Kristeen Cherney. The health benefits of CBD oil are being studied by world-class researchers We analyzed and summarized 17 of the best CBD studies of While this is not a comprehensive list, it does highlight some of the critical.