The problem many CBD vapers have faced recently seems to stem mainly from poor regulation over the vaping market in general, and the subsequent. There also are concerns about both the quality of CBD oil being need to be under the care of a health care provider who understands CBD. According to a report from the World Health Organization, “In humans, CBD exhibits no effects indicative of any abuse or dependence potential.
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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: 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.
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. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Cannabis und Cannabinoide in der Medizin: Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. Controlled clinical trial of cannabidiol in Huntington's disease.
Molecular targets of cannabidiol in neurological disorders. 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. How physicochemical properties of drugs affect their metabolism and clearance. New horizons in predictive drug metabolism and pharmacokinetics. Royal Society of Chemistry: Human metabolites of cannabidiol: Induction and genetic regulation of mouse hepatic cytochrome P by cannabidiol.
ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice. 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. Schurr A, Livne A. Differential inhibition of mitochondrial monoamine oxidase from brain by hashish components. Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxicischemic newborn piglets.
Acute and chronic administration of cannabidiol increases mitochondrial complex and creatine kinase activity in the rat brain. Inhibiting heat shock proteins can potentiate the cytotoxic effect of cannabidiol in human glioma cells.
Cannabidiol (CBD) may have some health benefits, and it may also pose risks. Products containing the compound are now legal in many. A first pilot study in healthy volunteers in by Mincis et al. administering 10 mg oral CBD for 21 days did not. Can cannabis keep you healthy? Get the facts on CBD oil, a natural product that may ease your anxiety and boost your heart health.